Dimethylformamide → 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbaldehyde
Reaction equation
P(Cl)(Cl)(Cl)=O.CN(C)[CH:8]=[O:9].[CH:11]1([CH2:17][N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH3:28])[CH:20]=[CH:19]2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.C(=O)(O)[O-].[Na+]>O>[CH:11]1([CH2:17][N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][C:25]=3[O:27][CH3:28])[C:20]([CH:8]=[O:9])=[CH:19]2)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1Participants
Conditions
- Temperature
- 0 °C
Procedure
Phosphorous oxychloride (12 ml, 0.13 mol) was added slowly over 30 minutes to dimethylformamide (30 ml) at −10° C. The solution was allowed to warm to 0° C. over 1 h, then 1-(cyclohexyl)methyl-7-methoxy-1H-indole (prepared as in Example 26; 3.2 g, 13 mmol) was added portionwise and the solution stirred at room temperature for 16 h. The solution was cooled in an ice bath and diluted with water, then neutralised carefully with sodium bicarbonate and extracted with ethyl acetate (3×50 ml). The organic extracts were combined and the solvent removed in vacuo. The residue (3.5 g) was dissolved in aqueous sodium hydroxide solution (5 M; 100 ml) and the mixture refluxed at 100° C. for a further 16 h. The solution was cooled and extracted with ethyl acetate (3×50 ml), the organic extracts combined and the solvent removed in vacuo to afford 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbaldehyde (2.2 g, 8.12 mmol) as a white solid.
Workup
- temperatureThe solution was cooled in an ice bath
- extractionextracted with ethyl acetate (3×50 ml)
- customthe solvent removed in vacuo
- dissolutionThe residue (3.5 g) was dissolved in aqueous sodium hydroxide solution (5 M; 100 ml)
- temperaturethe mixture refluxed at 100° C. for a further 16 h
- temperatureThe solution was cooled
- extractionextracted with ethyl acetate (3×50 ml)
- customthe solvent removed in vacuo
Sources & evidence
- ORD record
- ord-d0425844a8824adebce6acc1a4d119ae
- Source dataset
- uspto-grants-2010_04
- Patent number
- US07700634B2
Reaction notes
Loading…